Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention.

1.
Grier DG, Halliday HL: Effects of glucocorticoids on fetal and neonatal lung development. Treat Respir Med 2004;3:295-306.
2.
Halliday HL: Lung diseases: problems of steroid treatment of fetus and newborn; in Buonocore G, Bracci R, Weindling M (eds): Neonatology: A Practical Approach to Neonatal Diseases. Milan, Springer, 2016.
3.
Liggins GC, Howie RN: A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome in preterm infants. Pediatrics 1972;50:515-525.
4.
Roberts D, Dalziel S: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006;3:CD004454.
5.
Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A, Harding JE: Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in a randomised controlled trial. BMJ 2005;331:665-668.
6.
Baden M, Bauer CR, Colle E, Klein G, Taeusch HW Jr, Stern L: A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome. Pediatrics 1972;50:526-534.
7.
Taeusch HW Jr, Wang NS, Baden M, Bauer CR, Stern L: A controlled trial of hydrocortisone therapy in infants with respiratory distress syndrome: II. Pathology. Pediatrics 1973;52:850-854.
8.
Fitzhardinge PM, Eisen A, Lejtenyi C, Metrakos K, Ramsay M: Sequelae of early steroid administration to the newborn infant. Pediatrics 1974;55:877-883.
9.
Mammel MC, Green TP, Johnson DE, Thompson TR: Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia. Lancet 1983;1:1356-1358.
10.
Avery GB, Fletcher AB, Kaplan M, Brudno DS: Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia. Pediatrics 1985;75:106-111.
11.
Yeh TF, Lin YJ, Huang CC, Chen YJ, Lin CH, Lin HC, Hsieh WS, Lien YJ: Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics 1998;101:E7.
12.
Doyle LW, Ehrenkranz RA, Halliday HL: Early (<8 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2014;5: CD001146.
13.
Doyle LW, Ehrenkranz RA, Halliday HL: Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2014;5:CD001145.
14.
Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, et al; PREMILOC trial study group: Effect of early low dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016;387:1827-1836.
15.
Baud O, Biran V, Trousson C, Leroy E, Mohamed D, Alberti C: Two-year outcomes after prophylactic hydrocortisone in extremely preterm neonates. European Academy of Paediatric Societies Congress, Geneva, 2016. Eur J Pediatr 2016;175:1393-1880 (abstract 330).
16.
Peltoniemi OM, Lano A, Yliherva A, Kari MA, Hallman M; Neonatal Hydrocortisone Working Group: Randomised trial of early neonatal hydrocortisone demonstrates potential undesired effects on neurodevelopment at preschool age. Acta Paediatr 2016;105:159-164.
17.
Tu YF, Wang LW, Wang ST, Yeh TF, Huang CC: Postnatal steroids and febrile seizure susceptibility in preterm children. Pediatrics 2016;137:e20153404.
18.
Shah VS, Ohlsson A, Halliday HL, Dunn M: Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev 2012;5: CD001969.
19.
Bassler D, Halliday HL, Plavka R, Hallman M, Shinwell ES, Jarreau PH, et al: The Neonatal European Study of Inhaled Steroids (NEUROSIS): an EU-funded international randomised controlled trial in preterm infants. Neonatology 2010;97:52-55.
20.
Bassler D, Plavka R, Shinwell ES, Hallman M, Jarreau PH, Carnielli V, et al; NEUROSIS Trial Group: Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med 2015;373:1497-1506.
21.
Shah VS, Ohlsson A, Halliday HL, Dunn M: Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates. Cochrane Database Syst Rev 2017;1:CD001969.
22.
Shinwell ES, Portnov I, Meerpohl JJ, Karen T, Bassler D: Inhaled corticosteroids for bronchopulmonary dysplasia: a meta-analysis. Pediatrics 2016;138:e20162511.
23.
Shah SS, Ohlsson A, Halliday HL, Shah VS: Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev 2012;5: CD002058.
24.
Shah SS, Ohlsson A, Halliday HL, Shah VS: Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane Database Syst Rev 2012;5: CD002057.
25.
Yeh TF, Lin HC, Chang CH, Wu TS, Su BH, Li TC, Pyati S, Tsai CH: Early intracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics 2008;121:e1310-e1318.
26.
Kuo HT, Lin HC, Tsai CH, Chouc IC, Yeh TF: A follow-up study of preterm infants given budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants. J Pediatr 2010;156:537-541.
27.
Huang LT, Yeh TF, Kuo YL, Chen PC, Chen CM: Effect of surfactant and budesonide on pulmonary distribution of fluorescent dye in mice. Pediatr Neonatol 2015;56:19-24.
28.
Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC: Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med 2016;193:86-95.
29.
Bancalari E, Jain D, Jobe AH: Prevention of bronchopulmonary dysplasia: are intratracheal steroids with surfactant a magic bullet? Am J Respir Crit Care Med 2016;193:12-13.
30.
Roberts JK, Stockman C, Dahl MJ, Albertine KH, Egan E, Lin Z, Reilly CA, Ballard PL, Ballard RA, Ward RM: Pharmacokinetics of budesonide administered with surfactant in premature lambs: implications for neonatal clinical trials. Curr Clin Pharmacol 2016;11:53-61.
31.
Lin CH, Jeng MJ, Kuo BI, Kou YR: Effects of surfactant lavage combined with intratracheal budesonide instillation on meconium-injured piglet lungs. Pediatr Crit Care Med 2016;17:e287-e295.
32.
Bassler D: Inhalation or instillation of steroids for the prevention of bronchopulmonary dysplasia. Neonatology 2015;107:358-359.
33.
Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL: European consensus guidelines on the management of respiratory distress syndrome - 2016 update. Neonatology 2017;111:107-125.
34.
Halliday HL: Postnatal steroids: the way forward. Arch Dis Child Fetal Neonat Ed 2011;96:F158-F159.
35.
Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC: An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia. J Pediatr 2014;165:1258-1260.
36.
Virkud YV, Hornik CP, Benjamin DK, Laughon MM, Clark RH, Greenberg RG, Smith PB: Respiratory support for very low birth weight infants receiving dexamethasone. J Pediatr 2017;183:26-30.e3.
37.
Nuytten A, Behal H, Duhamel A, Jarreau PH, Mazela J, Milligan D, Gortner L, et al; EPICE Research Group: Evidence-based neonatal unit practices and determinants of postnatal corticosteroid-use in preterm births below 30 weeks GA in Europe: a population-based cohort study. PLoS One 2017;12:e0170234.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.